Referenced in: none

Automatically associated channels: Kv11.1 , Kv7.1 , Kv8.2

Title: Dual effect of phosphatidyl (4,5)-bisphosphate PIP2 on Shaker K+ channels.

Authors: Fayal Abderemane-Ali, Zeineb Es-Salah-Lamoureux, Lucie Delemotte, Marina A Kasimova, Alain J Labro, Dirk J Snyders, David Fedida, Mounir Tarek, Isabelle Baró, Gildas Loussouarn

Journal, date & volume: J. Biol. Chem., 2012 Oct 19 , 287, 36158-67

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22932893

Abstract
Phosphatidylinositol (4,5)-bisphosphate (PIP(2)) is a phospholipid of the plasma membrane that has been shown to be a key regulator of several ion channels. Functional studies and more recently structural studies of Kir channels have revealed the major impact of PIP(2) on the open state stabilization. A similar effect of PIP(2) on the delayed rectifiers Kv7.1 and Kv11.1, two voltage-gated K(+) channels, has been suggested, but the molecular mechanism remains elusive and nothing is known on PIP(2) effect on other Kv such as those of the Shaker family. By combining giant-patch ionic and gating current recordings in COS-7 cells, and voltage-clamp fluorimetry in Xenopus oocytes, both heterologously expressing the voltage-dependent Shaker channel, we show that PIP(2) exerts 1) a gain-of-function effect on the maximal current amplitude, consistent with a stabilization of the open state and 2) a loss-of-function effect by positive-shifting the activation voltage dependence, most likely through a direct effect on the voltage sensor movement, as illustrated by molecular dynamics simulations.